|
CD4/CD8 |
Plasmodium chabaudi chabaudi AS |
C57BL/6 |
anti-CD4 and anti-CD8 |
no |
no |
N.I. |
N.I. |
Increased peak and developed a high, persistent parasitemia |
Similar parasite-specific IgM early during infection and no IgG |
Süss et al., 1988, Infect Immun |
Link |
|
CD4/CD8 |
Plasmodium yoelii 17XNL |
CBA/CaJ |
anti-CD4 + adoptive transfer of immune CD8+ splenocytes |
no |
yes |
N.I. |
N.I. |
No parasite clearance |
N.I. |
Vinetz et al., 1990, J Immunol |
Link |
|
CD4/CD8/B cells |
Plasmodium yoelii 17XNL |
CBA/CaJ |
anti-CD4 + adoptive transfer of immune CD8+ and B+ splenocytes |
no |
yes |
N.I. |
N.I. |
No parasite clearance |
N.I. |
Vinetz et al., 1990, J Immunol |
Link |
|
CD40 |
Plasmodium berghei ANKA |
C57BL/6 |
CD40 -/- |
yes |
no (at the end of observation day 12) |
CM (100%) |
No CM |
Similar |
Prolonged survival (›day 12); ↓ thrombocytopenia and hypothermia; Brain: ↓ macrophage sequestration; no edema; ↑ TNF-a and ↓ ICAM-1 mRNA expression; Lung: ↓ macrophage sequestration; similar sequestration of pRBCs, PMNs and platelets; no edema; % pRBCs alveolar capillaries › % pRBCs in large blood vessels (similar to WT); ↑ TNF-a and ↓ ICAM-1; Spleen: similar splenomegaly, TNF-a and ↓ ICAM-1 mRNA expression |
Piguet et al., 2001, Am J Pathol |
Link |
|
CD40L |
Plasmodium berghei ANKA |
C57BL/6 |
CD40L -/- |
yes |
no (at the end of observation day 12) |
CM (100%) |
No CM |
Similar |
Prolonged survival (›day 12); ↓ thrombocytopenia and hypothermia; Brain: ↓ macrophage sequestration; ↓ TNF-a and ICAM-1 mRNA expression; ↑ TNF-a and ICAM-1 mRNA expression; Spleen: ↓ splenomegaly; ↑ TNF-a and ICAM-1 mRNA expression |
Piguet et al., 2001, Am J Pathol |
Link |
|
CD40L |
Plasmodium berghei ANKA |
C57BL/6J |
anti-CD40L |
yes |
N.I. |
CM (100%) |
N.I. |
Similar |
↓ thrombocytopenia and hypothermia; some mice had ↓ macrophage sequestration in brain whereas other mice had ↑ macrophage and lymphocyte sequestration |
Piguet et al., 2001, Am J Pathol |
Link |
|
CD40L |
Plasmodium berghei ANKA |
C57BL/6J |
anti-CD40L |
N.I. |
N.I. |
N.I. |
N.I. |
N.I. |
↓ thrombocytopenia and ↓ microparticles in plasma |
Piguet et al., 2002, Apoptosis |
Link |
|
CD41/CD61 (gpIIb/IIIa) |
Plasmodium berghei ANKA |
C57BL/6 |
anti-CD41 (early treatment) |
yes |
9% (at the end of observation day 12) |
CM (100%) |
CM (9%) |
Similar |
Prolonged survival; ↓ CD41+ platelets in circulation |
Sun et al., 2003, Infect Immun |
Link |
|
CD41/CD61 (gpIIb/IIIa) |
Plasmodium berghei ANKA |
C57BL/6 |
anti-CD41 (early treatment) |
yes |
12,5% (at the end of observation day 14) |
CM (100%) |
CM (12,5%) |
Similar |
Prolonged survival (not with late treatment); ↓ CD41+CD61+, CD41-CD61+ and similar CD41-CD61- platelets in circulation; ↑ plasma IL-10, IL-1a, IL-6, IFN-g, TNF-a, fibrinogen,↓ plasma IL-2 and similar plasma factor VII, TF and vWF |
Van der Heyde et al., 2005, Blood |
Link |
|
CD41/CD61 (gpIIb/IIIa) |
Plasmodium berghei ANKA |
C57BL/6 |
anti-CD61 (early treatment) |
yes |
60% (at the end of observation day 14) |
CM (100%) |
CM (60%) |
Similar |
↓ CD41+CD61+, CD41+CD61- and similar CD41-CD61- platelets in circulation |
Van der Heyde et al., 2005, Blood |
Link |
|
CD54 (ICAM-1) |
Plasmodium berghei ANKA |
CBA/Ca |
anti-ICAM-1 |
yes |
yes |
CM (100%) |
CM (100%) |
Similar |
N.I. |
Falanga et al., 1991, Eur J Immunol |
Link |
|
CD54 (ICAM-1) |
Plasmodium berghei ANKA |
C57BL/6 |
ICAM-1-/- |
yes |
yes |
CM (100%) |
CM (20%) |
Similar |
Prolonged survival (1-3 weeks); no neurologic symptoms; ↑ blood leukocytes and ↓ thrombocytopenia; ↓ serum TNF-a, similar serum IFN-g and NO3-; ↑ TNF-a mRNA expression in brain, similar TNF-a mRNA expression in lungs and spleen; similar VCAM expression in brain capillaries; similar macrophage accumulation in brain; ↓ macrophage, pRBC and similar PMN, platelet accumulation in lung |
Favre et al., 1999, Microbes Infect |
Link |
|
CD54 (ICAM-1) |
Plasmodium berghei ANKA |
CBA/Ca |
anti-ICAM-1 |
yes |
yes |
CM (100%) |
Toxicity or CM |
Similar |
Earlier death (hours after antibody injection) |
Grau et al., 1991, Eur J Immunol |
Link |
|
CD54 (ICAM-1) |
Plasmodium berghei ANKA |
CBA/Ca |
soluble ICAM-1 |
yes |
yes |
CM (100%) |
CM (100%) |
Similar |
Prolonged survival (days) |
Grau et al., 1991, Eur J Immunol |
Link |
|
CD54 (ICAM-1) |
Plasmodium berghei ANKA |
C57BL/6 |
ICAM-1-/- |
yes |
33% (at the end of observation day 14) |
CM (100%) |
CM (33%) |
Similar |
Prolonged survival (1-3 weeks); similar leukocyte rolling and adhesion in brain microvasculature; |
Li et al., 2003, J Investig Med |
Link |
|
CD54 (ICAM-1) |
Plasmodium berghei ANKA |
C57BL/6 |
ICAM-1-/- |
N.I. |
N.I. |
N.I. |
N.I. |
N.I. |
% pRBCs alveolar capillaries = % pRBCs in large blood vessels of lung (in contrast to WT) |
Piguet et al., 2001, Am J Pathol |
Link |
|
CD54 (ICAM-1) |
Plasmodium berghei ANKA |
C57BL/6 |
ICAM-1-/- |
N.I. |
N.I. |
N.I. |
N.I. |
N.I. |
↓ platelet rolling and adhesion in brain microvasculature |
Sun et al., 2003, Infect Immun |
Link |
|
CD62L (L-selectin, LECAM-1) |
Plasmodium berghei ANKA |
CBA/Ca |
anti-L-selectin |
yes |
yes |
CM (100%) |
CM (100%) |
Similar |
N.I. |
Falanga et al., 1991, Eur J Immunol |
Link |
|
CD62P (P-selectin) |
Plasmodium berghei ANKA |
C57BL/6 |
P-selectin -/- |
yes |
80% (at the end of observation day 14) |
CM (100%) |
CM (80%) |
Similar |
Prolonged survival (days); ↓leukocyte rolling and similar adhesion on the brain endothelium (also in uninfected P-selectin deficient mice compared to uninfected WT mice) |
Chang et al., 2003, Infect Immun |
Link |
|
CD62P (P-selectin) |
Plasmodium berghei ANKA |
C57BL/6 x 129/Sv |
P-selectin -/- |
yes |
yes |
CM (80%) |
CM (4.5 %) |
Similar |
Prolonged survival (2-3 weeks); no neurological symptoms; similar platelet and leukocyte sequestration in brain vessels; chimeric mice lacking endothelial P-selectin were protected whereas chimeric mice lacking platelet P-selectin showed symptoms of CM (57.1 %) |
Combes et al., 2004, Am J Pathol |
Link |
|
CD62P (P-selectin) |
Plasmodium berghei ANKA |
CBA/J |
anti-P-selectin |
yes |
yes |
CM (90%) |
CM (90%) |
Similar |
N.I. |
Combes et al., 2004, Am J Pathol |
Link |
|
CD62P (P-selectin) |
Plasmodium berghei ANKA |
C57BL/6 |
P-selectin -/- |
N.I. |
N.I. |
N.I. |
N.I. |
N.I. |
Similar thrombocytopenia |
Sun et al., 2003, Infect Immun |
Link |
|
CD8 |
Plasmodium berghei ANKA |
C57BL/6J |
anti-CD8 |
yes |
yes |
CM (100%) |
No CM |
Similar |
Prolonged survival (1-2 weeks); both early and late (prior to the onset of neurological symptoms) treatment inhibited CM |
Beghdadi et al., 2008, J Exp Med |
Link |
|
CD8 |
Plasmodium berghei ANKA |
C57BL/6J |
anti-CD8 (late treatment) |
yes |
yes |
CM (100%) |
No CM |
N.I. |
Prolonged survival (1-2 weeks) |
Belnoue et al., 2003, Infect Immun |
Link |
|
CD8 |
Plasmodium berghei ANKA |
129P2Sv/Ev |
anti-CD8 (late treatment) |
yes |
yes |
CM (60-100%) |
No CM |
N.I. |
N.I. |
Belnoue et al., 2008, Parasite Immunol. |
Link |
|
CD8 |
Plasmodium berghei ANKA |
129/Sv x C57BL/6 |
CD8 -/- |
yes |
yes |
CM (53%) |
No CM |
N.I. |
N.I. |
Boubou et al., 1999, Int Immunol |
Link |
|
CD8 |
Plasmodium berghei ANKA |
C57BL/6 |
anti-CD8 |
yes |
yes |
CM |
No CM |
Similar |
↓ Evans Blue leakage in brain, lungs, kidneys and heart; ↓ edema in brain, lungs and kidneys; no cracked skull; ↓ serum lactate, HCO3- and glutamate (similar to uninfected mice); ↑ blood pH (similar to normal); similar mean arterial blood flow; ↑ cardiac output (similar to uninfected mice) |
Chang et al., 2001, Infect Immun |
Link |
|
CD8 |
Plasmodium berghei ANKA |
C57BL/6J |
anti-CD8 |
yes |
yes |
CM (100%) |
No CM |
Delayed |
Prolonged survival (1-2 weeks); both early and late (prior to the onset of neurological symptoms) treatment inhibited CM; no neurological or respiratory symptoms |
Egima et al., 2007, Malar J |
Link |
|
CD8 |
Plasmodium berghei ANKA |
C57BL/6J |
anti-CD8 (early treatment) |
yes |
yes |
CM (94%) |
No CM |
Similar |
Prolonged survival (1-2 weeks); both early and late (prior to the onset of neurological symptoms) treatment inhibited CM |
Hermsen et al., 1997, Parasitology |
Link |
|
CD8 |
Plasmodium berghei ANKA |
C57BL/6 |
anti-CD8 |
yes |
yes |
CM (80%) |
No CM |
Transiently decreased 72 h post treatment |
Prolonged survival (1-2 weeks) when treated on the onset of CM; temporary improvement of clinical score; ↓ sequestration of pRBC that are transgenic for a luciferase gene |
Randall et al., 2008, Infect Immun |
Link |
|
CD8 |
Plasmodium berghei ANKA |
CBA |
anti-CD8 |
yes |
yes |
CM (100%) |
CM (30%) |
Similar |
Prolonged survival (1-2 weeks) when treated on the onset of CM; stabilization of clinical score; ↓ sequestration of pRBC that are transgenic for a luciferase gene |
Randall et al., 2008, Infect Immun |
Link |
|
CD8 |
Plasmodium berghei ANKA |
C57BL/6J |
anti-CD8 (early treatment) |
yes |
yes |
CM (100%) |
No CM |
Similar |
Prolonged survival (1-2 weeks) |
Yañez et al., 1996, J Immunol |
Link |
|
CD8 |
Plasmodium berghei ANKA |
C57BL/6J |
anti-CD8 (early treatment) |
yes |
yes |
CM (67%) |
No CM |
Similar |
N.I. |
Yañez et al., 1999, Infect Immun |
Link |
|
CD8 |
Plasmodium berghei ANKA |
C57BL/6J |
anti-CD8 (late treatment) |
yes |
yes |
CM (67%) |
CM (67%) |
Similar |
N.I. |
Yañez et al., 1999, Infect Immun |
Link |
|
CD8 |
Plasmodium berghei K173 |
C57BL/6J |
anti-CD8 (early treatment) |
yes |
yes |
CM (91%) |
CM (8%) |
Similar |
N.I. |
Hermsen et al., 1997, Parasitology |
Link |
|
CD8 |
Plasmodium berghei K173 |
C57BL/6J |
anti-CD8 (late treatment) |
yes |
yes |
CM (91%) |
CM (0-25%) |
Similar |
N.I. |
Hermsen et al., 1997, Parasitology |
Link |
|
CD8 |
Plasmodium berghei K173 |
C57BL/10 |
anti-CD8 (early treatment) |
yes |
yes |
CM (75%) |
CM (25%) |
Similar |
N.I. |
Hermsen et al., 1997, Parasitology |
Link |
|
CD8 |
Plasmodium berghei NK65 |
C57BL/6J |
anti-CD8 (late treatment) |
yes |
yes |
MA-ARDS (90%) |
Attenuated MA-ARDS |
N.I. |
↓ lung weight, alveolar edema and cellular infiltration |
Van den Steen et al., 2010, Am J Crit Care Med |
Link |
|
CD8 |
Plasmodium berghei NK65 |
CBA/JNCrj |
anti-CD8 |
yes |
yes |
N.I. |
N.I. |
Similar |
Prolonged survival (1-2 weeks) |
Waki et al., 1992, Immunology |
Link |
|
CD8 |
Plasmodium berghei XAT |
CBA/JNCrj |
anti-CD8 |
no |
no |
N.I. |
N.I. |
Similar |
Resistant to P. berghei NK65 challenge infection |
Waki et al., 1992, Immunology |
Link |
|
CD8 |
Plasmodium chabaudi chabaudi AS |
C57BL/6 |
anti-CD8 |
N.I. |
N.I. |
N.I. |
N.I. |
N.I. |
↓ serum IFN-g |
Meding et al., 1990, Infect Immun |
Link |
|
CD8 |
Plasmodium chabaudi chabaudi AS |
C57BL/6NCrlBR |
anti-CD8 |
no |
no |
N.I. |
N.I. |
Similar peak and developed 2 major recrudescences |
The 2 major recrudescendes coincided with the ↑ level of reticulocytosis, which returned to normal level when the parasites were cleared from the circulation |
Podoba et al., 1991, Infect Immun |
Link |
|
CD8 |
Plasmodium chabaudi chabaudi AS |
C57BL/6 |
anti-CD8 |
no |
no |
N.I. |
N.I. |
Slightly increased peak |
Similar parasite-specific IgM and IgG |
Süss et al., 1988, Infect Immun |
Link |
|
CD8 |
Plasmodium yoelii 17XNL |
C57BL/6 |
anti-CD8 |
no |
yes (~20%) |
N.I. |
N.I. |
N.I. |
N.I. |
Butler et al., 2012, Nat Immunol |
Link |
|
CD8 |
Plasmodium yoelii 17XNL |
BALB/c |
anti-CD8 |
no |
no |
N.I. |
N.I. |
Similar |
N.I. |
Vinetz et al., 1990, J Immunol |
Link |
|
CD8+ T cell/CD1d-restricted NKT cells |
Plasmodium berghei ANKA |
C57BL/6 |
b2 microglobuline -/- |
N.I. |
N.I. |
N.I. |
N.I. |
Similar on day 5 |
Prolonged survival (days) |
Nie et al., 2009, PLoS Pathog |
Link |
|
CD8+ T cell/CD1d-restricted NKT cells |
Plasmodium berghei ANKA |
C57BL/6 |
b2 microglobuline -/- |
yes |
yes |
CM (94%) |
No CM |
N.I. |
N.I. |
Yañez et al., 1996, J Immunol |
Link |
|
CD8+ T cell/CD1d-restricted NKT cells |
Plasmodium berghei K173 |
C57BL/6 |
b2 microglobuline -/- |
N.I. |
N.I. |
N.I. |
N.I. |
N.I. |
Plasma IFN-g and splenic IFN-g mRNA expression 24h p.i. was abrogated |
Mitchell et al., 2005, Infect Immun |
Link |
|
CD8+ T cell/CD1d-restricted NKT cells |
Plasmodium berghei NK65 |
C57BL/6 |
b2 microglobuline -/- |
yes |
yes |
Liver pathology |
Liver pathology |
N.I. |
Similar liver injury, serum ALT levels, hepatic DX5+CD3+ cells; similar cytotoxicity by hepatic lymphocytes against hepatocytes |
Adachi et al., 2004, Int Immunol |
Link |
|
CD8+ T cell/CD1d-restricted NKT cells/IP-10 |
Plasmodium berghei ANKA |
C57BL/6 |
b2 microglobuline -/- + anti-IP-10 |
N.I. |
N.I. |
N.I. |
N.I. |
Decreased on day 5 |
Prolonged survival (days) |
Nie et al., 2009, PLoS Pathog |
Link |
|
CD80 |
Plasmodium chabaudi chabaudi AS |
NIH |
anti-CD80 |
no |
no |
N.I. |
N.I. |
Similar |
Similar IFN-g and IL-4 production by splenic T cells in vitro; similar IgG1 and similar IgG2a |
Taylor-Robinson et al., 1999, Immunology |
Link |
|
CD80/CD86 |
Plasmodium chabaudi chabaudi AS |
NIH |
anti-CD80 and anti-CD86 |
no |
N.I. |
N.I. |
N.I. |
Decreased peak and developed a chronic, low parasitemia (~1%) |
↑ IFN-g production by splenic T cells in vitro compared to anti-CD86 treatment alone, ↓ IL-4 production by splenic T cells in vitro; ↓ IgG1 |
Taylor-Robinson et al., 1999, Immunology |
Link |
|
CD86 |
Plasmodium chabaudi chabaudi AS |
NIH |
anti-CD86 |
no |
N.I. |
N.I. |
N.I. |
Developed a chronic low parasitemia (~1%) |
↑ IFN-g and abrogation of IL-4 production by splenic T cells in vitro; ↓ IgG1 and similar IgG2a |
Taylor-Robinson et al., 1999, Immunology |
Link |
|
Class A type I and II macrophage scavenger receptors |
Plasmodium chabaudi AS |
C57BL/6 |
SR-AI/II -/- |
no |
no |
N.I. |
N.I. |
Similar |
Similar phagocytosis of pRBCs and free merozoites by peritoneal macrophages |
Su et al., 2002, J Infect Dis |
Link |
|
COX-1/2 |
Plasmodium berghei ANKA |
ICR |
COX1/COX2 inhibitor (aspirin) |
yes |
yes |
CM (85%) |
CM (100%) |
Similar |
Slightly earlier death; similar mRNA expression of 5-lipoxygenase in brain and spleen; mRNA of phospholipase A2 similar in brain and ↑ on day 12 in spleen; mRNA expression of COX-1 and COX-2 was similar in spleen and ↓ in brain 7 days p.i.; ↑ serum leukotriene B4 levels |
Xiao et al., 1999, Am J Trop Med Hyg |
Link |
|
COX-1/2 |
Plasmodium berghei K173 |
C57BL/6J |
non-selective COX-1/2 inhibitor (indomethacin) |
yes |
yes |
CM (58%) |
CM (62%) |
Similar |
N.I. |
Blok et al., 1992, J Infect Dis |
Link |
|
COX-2 |
Plasmodium berghei ANKA |
CBA |
selective COX-2 inhibitor (celecoxib) |
yes |
yes |
CM |
CM |
Similar |
Earlier death (~days); earlier onset of cerebral symptoms (eg. edema, seizures);↓ bicycle-PGE2 level in brain (not in uninfected treated mice); similar brain mRNA expression of IL-10, 5-lipoxygenase and 5-lipoxygenase activating protein (FLAP) |
Ball et al., 2004, J Infect Dis |
Link |
|
COX-2 |
Plasmodium berghei K173 |
CBA |
selective COX-2 inhibitor (celecoxib) |
yes |
yes |
HP&A |
HP&A |
Similar |
No induction of cerebral symptoms, similar progression of infection |
Ball et al., 2004, J Infect Dis |
Link |
|
CRP |
Plasmodium berghei ANKA |
C57BL/6J |
CRP-tg |
yes |
N.I. |
CM (100%) |
No CM |
Decreased |
N.I. |
Aggrey et al., 2013, J Immunol |
Link |
|
CRP |
Plasmodium yoelii |
C57BL/6J |
CRP-tg |
N.I. |
N.I. |
N.I. |
N.I. |
Decreased |
N.I. |
Aggrey et al., 2013, J Immunol |
Link |
|
CTLA-4 |
Plasmodium berghei ANKA |
BALB/cAnNCrl |
anti-CTLA-4 |
yes |
yes |
CM (~30%) |
CM (100%) |
Similar |
↑ numbers of CD8+ T cells in the brain; ↑ frequency of brain petechial hemorrhages; ↑ proportion of vessels plugged with iRBCs; ↑ numbers of pigmented (parasite-containing) macrophages in the liver; ↑ whole body, head and isolated brain parasite burdens (↑ bioluminescence of luciferase-expressing parasites); ↑ proportion of activated CD4+ and CD8+ T cells in the spleen; ↑ plasma IFN-g, TNF, IL-6, IL-10 and MCP-1/CCL2; ↑ secretion of IFN-g and IL-10 by stimulated CD4+ T cells and ↑ IFN-g secretion by stimulated CD8+ T cells; |
Hafalla et al., 2012, PLoS Pathog |
Link |
|
CTLA-4 |
Plasmodium berghei ANKA |
C57BL/6 |
anti-CTLA-4 |
yes |
yes |
No CM |
CM (100%) |
Similar |
Earlier death (~2 weeks); ↑ weight loss; induction of neurological symptoms; no ↓ CD4+ T cells in spleen 5 days p.i.; ↑ spontaneous and anti-CD3 induced proliferation of spleen cells taken on day 5 p.i. But not from day 8 p.i.; similar IFN-g and ↑ NO production by anti-CD3 stimulated spleen cells 8 days p.i.; ↑ pathology and hemozoin deposition in liver |
Jacobs et al., 2002, J Immunol |
Link |
|
CTLA-4 |
Plasmodium berghei ANKA |
C57BL/6 |
anti-CTLA-4 |
yes |
yes |
Moderate liver pathology |
↑ Liver pathology |
Similar |
↑ serum ALT and AST; ↑ weight loss; ↑ CD4+ and CD8+ T cells and similar gd T cells in liver parenchyma 8 days p.i.; ↑ and similar number of IFN-g producing cells in liver and spleen, respectively; similar and ↑ proliferation of liver and spleen cells, respectively |
Jacobs et al., 2004, Eur J Immunol |
Link |
|
CTLA-4 |
Plasmodium yoelii 17XL |
BALB/c |
anti-CTLA-4 (day 0) |
30% |
70% |
N.I. |
Liver pathology |
Similar |
↑ serum ALT and AST levels (↑ liver pathology); ↑ weight loss; ↑ % CD25+ CD4+, CD62Llow CD4+ and CD69+ CD4+ T cells in spleen; similar IL-12p40 and ↑ IFN-g, TNF-a, IL-4 and IL-10 in serum |
Lepenies et al., 2007, Microbes Infect |
Link |
|
CTLA-4 |
Plasmodium yoelii 17XNL |
BALB/c |
anti-CTLA-4 (day 0) |
20% |
30% |
N.I. |
N.I. |
Decreased peak and earlier clearance |
Similar serum ALT and AST levels; similar body weight; ↑ % CD25+ CD4+, CD62Llow CD4+ and CD69+CD4+ T cells in spleen; similar IL-12p40 and TNF-a and ↑ IFN-g, IL-4 and IL-10 in serum |
Lepenies et al., 2007, Microbes Infect |
Link |
|
CTLA-4/CD4 |
Plasmodium berghei ANKA |
BALB/cAnNCrl |
anti-CTLA-4 + anti-CD4 |
yes |
yes |
CM (~30%) |
CM (% depended on the time of administration) |
N.I. |
Early CD4 depletion delayed the onset of CM |
Hafalla et al., 2012, PLoS Pathog |
Link |
|
CTLA-4/CD4 |
Plasmodium berghei ANKA |
C57BL/6 |
anti-CTLA-4 + anti-CD4 |
yes |
yes |
No CM |
No CM |
N.I. |
N.I. |
Jacobs et al., 2002, J Immunol |
Link |
|
CTLA-4/CD8 |
Plasmodium berghei ANKA |
BALB/cAnNCrl |
anti-CTLA-4 + anti-CD8 |
yes |
yes |
CM (~30%) |
No CM |
N.I. |
N.I. |
Hafalla et al., 2012, PLoS Pathog |
Link |
|
CTLA-4/IFN-g |
Plasmodium berghei ANKA |
BALB/cAnNCrl |
anti-CTLA-4 + anti-IFN-g |
yes |
yes |
CM (~30%) |
No CM |
N.I. |
N.I. |
Hafalla et al., 2012, PLoS Pathog |
Link |
|
CTLA-4/TNF |
Plasmodium berghei ANKA |
BALB/cAnNCrl |
anti-CTLA-4 + anti-TNF |
yes |
yes |
CM (~30%) |
CM (~80%) |
N.I. |
N.I. |
Hafalla et al., 2012, PLoS Pathog |
Link |
|
CXCL10 (IP-10) |
Plasmodium berghei ANKA |
C57BL/6 |
CXCL10 -/- |
90% (at the end of observation day 20) |
40% (at the end of observation day 20) |
CM (90%) |
CM (40%) |
N.I. |
N.I. |
Campanella et al., 2008, Proc Natl Acad Sci U S A |
Link |
|
CXCL10 (IP-10) |
Plasmodium berghei ANKA |
C57BL/6 |
CXCL10 -/- |
yes |
5% (at the end of observation day 20) |
CM (100%) |
CM (5%) |
Decreased |
Prolonged survival (at least until day 20); no neurological symptoms; ↓ blood vessels with intravascular inflammation; ↓ pRBC, CD4+ and CD8+ T cell sequestration (similar NK cells); similar ICAM-1+ blood vessels; ↑ parasite-specific proliferation and IFN-g production by CD4+ T cells; ↑ number of CXCR3+/IFN-g+CD4+ and CXCR3+/IFN-g+CD8+ T cells in spleen; ↓ IFN-g in serum; anti-IFN-g treatment had no effect on reduced parasitemia |
Nie et al., 2009, PLoS Pathog |
Link |
|
CXCL10 (IP-10) |
Plasmodium berghei ANKA |
C57BL/6 |
anti-CXCL10 (d3-9) |
yes |
20% (at the end of observation day 20) |
CM (100%) |
CM (20%) |
Decreased on day 5 |
Prolonged survival (at least until day 20); no neurological symptoms; ↓ blood vessels with intravascular inflammation; similar pRBC sequestration and ↓ CD4+ and CD8+ T cells (similar NK cells); majority of brain infiltrating T cells were CXCR3+ and CCR5-, indicating that other CXCR3 chemokines (MIG and I-TAC) can still recruit CXCR3+ T cells to the brain; similar expression of CD25 and CD69 activation markers in brain sequestering T cells and cells could still migrate to recombinant IP-10 in a chemotaxis assay; ↑ parasite-specific proliferation of CD4+ T cells; similar number of CXCR3+/IFN-g+CD4+ and CXCR3+/IFN-g+CD8+ T cells in spleen |
Nie et al., 2009, PLoS Pathog |
Link |
|
CXCL10 (IP-10) |
Plasmodium berghei ANKA |
C57BL/6 |
anti-CXCL10 (d5-9) |
yes |
50% (at the end of observation day 17) |
CM (100%) |
CM (50%) |
N.I. |
Prolonged survival (at least until day 17); no neurological symptoms |
Nie et al., 2009, PLoS Pathog |
Link |
|
CXCL12 (SDF-1a) |
Plasmodium berghei ANKA |
C57BL/6 |
SDF-1a |
N.I. |
N.I. |
N.I. |
N.I. |
Decreased |
N.I. |
Garnica et al., 2002, Immunol lett |
Link |
|
CXCL12 (SDF-1a) |
Plasmodium berghei ANKA |
BALB/c |
SDF-1a |
N.I. |
N.I. |
N.I. |
N.I. |
Decreased |
N.I. |
Garnica et al., 2002, Immunol lett |
Link |
|
CXCL12 (SDF-1a) |
Plasmodium berghei ANKA |
BALB/c |
SDF-1a |
N.I. |
N.I. |
N.I. |
N.I. |
Decreased |
Similar number of CD11c+ cells in the bone marrow 14 days p.i.; ↑ numbers of cd11c+CD8a+ and CD11c+CD11b+ cells in the spleen 14 days p.i.; induction of periarteriolar CD11c clustering in the spleen |
Garnica et al., 2005, Immunology |
Link |
|
CXCL4 (PF-4) |
Plasmodium berghei ANKA |
C57BL/6 |
PF-4 -/- |
70% (at the end of observation day 10) |
30% (at the end of observation day 10) |
CM (70%) |
CM (30%) |
Similar |
No neurological symptoms; no ↑ plasma TNF-a or IFN-g 5 days p.i.; no ↑ CXCR3 expression by splenocyt-derived T cells; no↑ number of CD4+ or CD8+ T cells in brain |
Srivastava et al., 2008, Cell Host Microbe |
Link |
|
CXCL4 (PF-4) |
Plasmodium berghei ANKA |
PF4 -/- |
rPF-4 |
30% (at the end of observation day 10) |
80% (at the end of observation day 10) |
CM (30%) |
CM (80%) |
Similar |
N.I. |
Srivastava et al., 2008, Cell Host Microbe |
Link |
|
CXCL4 (PF-4) |
Plasmodium berghei ANKA |
C57BL/6 |
PF-4 -/- |
N.I. |
N.I. |
N.I. |
N.I. |
N.I. |
↓ KLF4 expression in monocytes; ↓ monocytes in brain during CM |
Srivastava et al., 2010, PLoS ONE |
Link |
|
CXCL9 (MIG) |
Plasmodium berghei ANKA |
C57BL/6 |
CXCL9 -/- |
90% (at the end of observation day 20) |
40% (at the end of observation day 20) |
CM (90%) |
CM (40%) |
N.I. |
N.I. |
Campanella et al., 2008, Proc Natl Acad Sci U S A |
Link |
|
CXCR3 |
Plasmodium berghei ANKA |
CXCR3 -/- |
adoptive transfer of in vivo activated WT splenocytes or CD8+ T cells (day 0) |
30% (at the end of observation day 20) |
70-90% (at the end of observation day 20) |
CM (30%) |
CM (70-90%) |
N.I. |
↑ number of WT (adoptively transferred) and CXCR3 -/- (own) CD8+ T cells in brain at the CM stage; ↑ IP-10, MIG, RANTES, MCP-1 and IFN-g mRNA expression in brain (similar to WT mice) |
Campanella et al., 2008, Proc Natl Acad Sci U S A |
Link |
|
CXCR3 |
Plasmodium berghei ANKA |
C57BL/6 |
in vitro activated WT and CXCR3 -/- effector CD8+ T cells (day 5) |
yes |
yes |
CM |
CM |
N.I. |
Similar number of WT and CXCR3 -/- cells in spleen and ↓ number of CXCR3 -/- cells in brain after competitive (co)transfer in WT mice |
Campanella et al., 2008, Proc Natl Acad Sci U S A |
Link |
|
CXCR3 |
Plasmodium berghei ANKA |
C57BL/6 |
CXCR3 -/- |
90% (at the end of observation day 23) |
10-30% (at the end of observation day 23) |
CM (90%) |
CM (10-30%) |
Similar |
Prolonged survival (1–3 weeks); no neurological symptoms; ↓ CD8+ T cells and NK cells and similar NKT cells in the brain; ↓ CXCL9 (MIG), CXCL10 (IP-10), CCL5 (RANTES), CCL2 (MCP-1) and IFN-g expression in the brain |
Campanella et al., 2008, Proc Natl Acad Sci U S A |
Link |
|
CXCR3 |
Plasmodium berghei ANKA |
CXCR3 -/- |
adoptive transfer of in vivo activated WT splenocytes or CD8+ T cells (day 0) |
yes |
yes |
CM (100%) |
CM (70%) |
N.I. |
N.I. |
Miu et al., 2008, J Immunol |
Link |
|
CXCR3 |
Plasmodium berghei ANKA |
C57BL/6 |
CXCR3 -/- |
yes |
yes |
CM (100%) |
CM (32%) |
Similar |
Prolonged survival (1–3 weeks); no neurological symptoms or recovered from neurological symptoms; ↓ CXCL9 (MIG), CXCL10 (IP-10) and CCL5 (RANTES) mRNA expression in the brain; ↓ sequestered CD8+ T cells and CD4+ T cells, similar NK, NKT and CD11b+ cells in the brain; ↓ IP-10, perforin, FasL, IFN-g and LT-a and similar ICAM-1 mRNA expression in the brain; similar IFN-g mRNA expression in the spleen |
Miu et al., 2008, J Immunol |
Link |
|
CXCR3 |
Plasmodium berghei ANKA |
C57BL/6 |
CXCR3 -/- |
70% (at the end of observation day 10) |
no (at the end of observation day 10) |
CM (70%) |
None (at the end of observation day 10) |
N.I. |
No neurological symptoms; no ↑ plasma TNF-a or IFN-g 5 days p.i.; no↑ number of CD4+ or CD8+ T cells in brain |
Srivastava et al., 2008, Cell Host Microbe |
Link |
|
CXCR4 |
Plasmodium chabaudi chabaudi CR |
C57BL/6 |
CXCR4 antagonist |
N.I. |
N.I. |
N.I. |
N.I. |
Increased recrudescences |
N.I. |
Garnica et al., 2002, Immunol lett |
Link |
|
Cystamine (CysH) |
Plasmodium chabaudi chabaudi AS |
A/J |
+ cystamine hydrochloride (prophylactic treatment) |
yes (100%) |
♂ yes (~60%); ♀ yes (~25%) |
N.I. |
N.I. |
Decreased |
N.I. |
Min-Oo et al., 2010, Exp Parasitol |
Link |
|
Cysteamine (CysH) |
Plasmodium chabaudi chabaudi AS |
A/J |
+ cysteamine hydrochloride + a suboptimal dose of artesunate or dihydroartemisinin |
yes |
No |
N.I. |
N.I. |
Delayed onset and decreased |
Dose-dependent synergistic antimalarial effect; dose-dependent effect on survival; ↓ disease symptoms |
Min-Oo et al., 2010, Antimicrob Agents Chemother |
Link |
|
Cysteamine (CysH) |
Plasmodium chabaudi chabaudi AS |
C57BL/6 |
+ cysteamine hydrochloride |
No |
No |
N.I. |
N.I. |
Decreased on days 5-7 |
Antimalarial effect is less strong compared to known antimalarial drugs |
Min-Oo et al., 2010, Antimicrob Agents Chemother |
Link |
|
Cysteamine (CysH) |
Plasmodium chabaudi chabaudi AS |
C57BL/6 |
+ cysteamine hydrochloride + a suboptimal dose of artesunate |
No |
No |
N.I. |
N.I. |
Delayed onset and decreased peak, no recrudescences |
Synergistic antimalarial effect; ↓ disease symptoms |
Min-Oo et al., 2010, Antimicrob Agents Chemother |
Link |
|
Cysteamine (CysH) |
Plasmodium chabaudi chabaudi AS |
A/J |
+ cysteamine hydrochloride (prophylactic treatment) |
yes (100%) |
yes (20%) |
N.I. |
N.I. |
Delayed onset and decreased |
Dose-dependent antimalarial effect; dose-dependent effect on survival |
Min-Oo et al., 2010, Exp Parasitol |
Link |
|
Cysteamine (CysH) |
Plasmodium chabaudi chabaudi AS |
A/J |
+ cysteamine hydrochloride (therapeutic treatment) |
♂ yes (100%); ♀ yes (35%) |
♂ yes (33-65%); ♀ yes (65-0%) |
N.I. |
N.I. |
Delayed onset and decreased |
The antimalarial effect and the effect on survival deminished when the onset of treatment was delayed; delayed ↑ of serum IFN-g and CCL2 (MCP-1) levels, ↓ serum CCL5 (RANTES) levels on d7 p.i., and similar serum levels of TNF, CCL4 (MIP-1b) and IL-10 |
Min-Oo et al., 2010, Exp Parasitol |
Link |
|
Cytidine deaminase AID (Aicda)/Ig heavy chain µ-secretory domein |
Plasmodium yoelii 17XNL |
C57BL/6 |
Aicda -/- (mature B cells which produce IgM, but they cannot undergo isotype switching or secrete Abs) |
no |
yes (100%) |
N.I. |
N.I. |
N.I. |
Therapeutic blockade of PD-L1 and LAG-3 did not improve parasite clearance |
Butler et al., 2012, Nat Immunol |
Link |
|
EPO |
Plasmodium berghei ANKA |
C57BL/6 |
rHuEpo |
yes |
yes |
CM |
less CM |
N.I. |
Improved survival; reversed clinical symptoms of CM; reduced brain hypoxia |
Hempel et al., 2011, Am J Pathol |
Link |
|
EPO |
Plasmodium berghei ANKA |
CBA/J |
rHuEpo |
yes |
yes |
CM (93%) |
CM (40%) |
Similar |
Similar body weight loss and anemia; ↓ number of ring hemorrhages in the brain; ↓ and delayed TNF and IFN-g and similar caspase-3, caspase-8, TNFR1, TNFR2 and IFN-gR mRNA expression in the brain; similar blood NO levels |
Kaiser et al., 2006, J Infect Dis |
Link |
|
EPO |
Plasmodium berghei ANKA |
C57BL/6J |
rHuEpo |
yes |
% depended on the time and dose of administration |
CM (93%) |
CM (% depended on the time and dose of administration) |
Similar |
↑ packed cell volume levels; recovered from hypothermia at the time point when untreated mice succumbed; ↓ IL-1b, TNF, IFN-g and similar caspase-1, caspase-3 and LT mRNA expression in the brain; ↓ number of apoptotic neurons in the brain |
Wiese et al., 2008, Malar J |
Link |
|
EPO |
Plasmodium chabaudi AS |
C57BL/6 |
anti-hEpo |
no |
yes (~70%) |
N.I. |
SMA (~70%) |
Similar |
Prolonged severe anemia; delayed induction of reticulocytosis |
Chang et al., 2004, J Infect Dis |
Link |
|
EPO |
Plasmodium chabaudi AS |
A/J |
rmEpo |
yes |
yes |
SMA (100%) |
SMA (100%) |
Similar |
Similar anemia |
Chang et al., 2004, J Infect Dis |
Link |